Postexposure prophylaxis (PEP) is routinely recommended following occupational exposure to HIV. Most PEP regimens involve the use of 2 nucleoside reverse transcriptase inhibitors with or without the addition of a protease inhibitor. PEP is also increasingly being prescribed following nonoccupational exposure to HIV. It is important that careful risk assessment be performed before prescribing PEP in both the occupational and nonoccupational settings and that risk reduction measures be emphasized.